OTSC assisted EFTR for the treatment of GIST: 40 cases analysis.

BACKGROUND AND AIMS: To verify the safety and efficacy of over-the-scope clip (OTSC)-assisted endoscopic full-thickness resection (EFTR) for the excision of stromal tumors. MATERIAL AND METHODS: Forty patients with gastric stromal tumors treated in the Department of Gastroenterology, Binzhou Medical University Hospital from December 2015 to March 2017 were included in this study. The surgical procedures included marking the lesion boundaries, cutting open the top surface of the lesion, installing an OTS, sucking the lesion into the transparent cap of the anatomical clip which was then released, application of an endoloop for EFTR, and confirming the complete resection and pathological examination of the lesion. Statistical analysis of the tumor site and size, operation time, success rates, complications, pathological examination results, and follow-up status was performed. RESULTS: The average operation duration was 38.40 ± 24.9 min. Three cases had an incomplete resection, but the lesion was later found to have fallen off together with the OTSC. Therefore, the treatment success rate was 100%. Postoperative pathological examination revealed leiomyomas in four cases and stromal tumors in the remaining 36 cases. CONCLUSIONS: OTSC-assisted EFTR is safe and effective for resection of gastrointestinal stromal tumors, especially for those <20 mm in size.

Diagnosis of gastric duplication cyst by positron emission tomography/computed tomography: A case report.

BACKGROUND: Gastric duplication cysts (GDCs) are extremely uncommon lesions and the definitive diagnosis of GDCs is challenging for gastrointestinal specialists. It is important that a differential diagnosis is performed to rule out the possibility of other diseases, mainly malignancies with a cystic component. Despite the use of multiple diagnostic modalities including endoscopy, the preoperative diagnosis of GDCs is challenging. CASE SUMMARY: A 53-year-old female patient with a GDC was confirmed by positron emission tomography/computed tomography (PET/CT) instead of more conventional procedures such as endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA). We propose that 18F-FDG-PET/CT has higher accuracy than EUS-FNA and may be an effective technique for the characterization of duplication cysts. CONCLUSION: Preoperative diagnosis of GDCs in adults is difficult largely due to their rarity and the absence of characteristic findings. In addition, few endoscopists include GDCs in the differential diagnosis when they encounter a lesion with cystic characteristics. 18F-FDG-PET/CT with additional imaging data, may complement EUS-FNA in the diagnosis of GDCs.

Farnesoid X receptor agonist INT-767 attenuates liver steatosis and inflammation in rat model of nonalcoholic steatohepatitis.

INTRODUCTION: Nonalcoholic steatohepatitis (NASH) is largely driven by the dysregulation of liver metabolism and inflammation. Bile acids and their receptor Farnesoid X receptor (FXR) play a critical role in the disease development. Here, we investigated whether INT-767, the newly-identified dual FXR/TGR5 agonist, can protect rat from liver injury during NASH. MATERIALS AND METHODS: NASH model was established by feeding the male SD rats with high-fat diet for 16 weeks. INT-767 was given by gavage to NASH rats from week 13 to week 16. At the end of 16 weeks, liver and serum were harvested, and bile acids, glucose and lipid metabolism, liver injury and histological features were evaluated. RESULTS: INT-767 treatment significantly alleviates high-fat caused liver damage characterized with lipid accumulation and hepatic infiltration of immune cells. INT-767 robustly restores the lipid, glucose metabolism to normal level, attenuates insulin resistance through upregulating FXR level and reverting the dysregulation of its target genes in liver metabolism. Molecularly INT-767 also attenuates the pro-inflammatory response by suppression of TNF-α and NF-κB signaling pathway. CONCLUSION: INT-767 may be an attractive candidate for a potential novel strategy on the treatment of NASH.

Correlation of endoscopic images and histological findings of a high grade dysplasia developed in a gastric xanthoma.

Gastric neoplasia developed in a xanthoma is very rare. We herein report a high grade dysplasia (HGD) arising in a gastric xanthoma removed by endoscopic submucosal dissection (ESD). A 57-year-old man was referred to our hospital for removal of rectal polyps. During surveillance esophago-gastro-duodenoendoscopy before polypectomy, an irregularly shaped gastric xanthoma with unusual color was found in the stomach. Although, magnifying narrow band imaging showed no typical neoplastic vessel or surface pattern on the surface and endoscopic biopsies revealed no tumor, diagnostic ESD was performed because of its irregular shape and unusual color for a commonly seen xanthoma. Histologically, a high grade dysplasia, 6 mm×6 mm in size, was detected within a gastric xanthoma. This is the first report of correlation of endoscopic images and histological findings of a HGD in a gastric xanthoma.

Overexpression of NDUFA4L2 is associated with poor prognosis in patients with colorectal cancer.

BACKGROUND: NDUFA4L2 (NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4-like 2, also called NADH-ubiquinone oxidoreductase MLRQ subunit homologue) was clearly enriched in the mitochondrial fraction under hypoxic conditions, and immunofluorescence showed a clear colocalization of NDUFA4L2 and cytochrome c in some tumour cells. However, little study has investigated its prognostic value in colorectal cancer (CRC). METHODS: In our study, mRNA-NDUFA4L2 and protein expression were analysed in 150 cases of CRC and adjacent normal tissues using immunohistochemistry, semi-quantitative reverse transcriptase-polymerase chain reaction. The correlation between NDUFA4L2 expression and clinicopathological factors was evaluated by the Chi-square test. Overall survival of patients was analysed by the Kaplan-Meier method. RESULTS: NDUFA4L2 overexpression was observed in 84% (126/150) of CRC tissues, but only in 24.7% (37/150) of adjacent normal tissues (P < 0.05). Semi-quantitative reverse transcriptase-polymerase chain reaction showed average mRNA expression levels to be 23.34 ± 1.356 and 4.34 ± 1.132 for CRC tissue and adjacent normal tissue (P < 0.05). Statistical analysis showed a significant correlation of NDUFA4L2 expression with histological grade, Dukes' stages, lymph node metastasis and liver metastasis. More importantly, multivariate analysis indicated that overexpression of NDUFA4L2 was an independent prognostic factor for CRC patients (P = 0.002). NDUFA4L2-negative patients had a higher tumour-free/overall survival rate than patients with high NDUFA4L2 expression (P = 0.001 and 0.002, respectively). CONCLUSIONS: Our data suggest that NDUFA4L2 overexpression is associated with tumour progression and a poor prognosis in CRC patients.

Discoidin domain receptors (DDRs): potential implications in atherosclerosis.

Atherosclerosis, one of the most common causes of cardiovascular diseases, is associated with a high morbidity and mortality. It is known that inflammation, vascular smooth muscle cell (VSMCs) phenotypic modulation and atheroma plaque vulnerability are main pathological characteristics of atherosclerosis. The discoidin domain receptors (DDRs), as unique collagen-binding tyrosine kinase receptors, were reported to be involved in the above pathogenesis process of atherogenesis. DDRs were detected on a series of cells within atherosclerotic plaques including macrophages, T cells and smooth muscle cells, and regulated the behaviors of these cells, implicating the potential involvement of DDRs in atherosclerosis. Herein we discuss the roles of DDRs in atherosclerosis, in an attempt to evaluate the value of DDRs as a therapeutic target for atherosclerosis.

Protective effects of SP600125 in a diet-induced rat model of non-alcoholic steatohepatitis.

OBJECTIVE. To investigate the protective effect of SP600125, a selective c-Jun N-terminal kinase inhibitor, in a diet-induced rat model of non-alcoholic steatohepatitis (NASH). MATERIAL AND METHODS. Sprague-Dawley rats were randomly divided into three groups: a normal control group (NC group), a high-fat model group (HF group) and an SP600125 treatment group (SP group). All animals were subjected to a percutaneous superior mesenteric vein retention catheter operation and fed with a standard diet for 10 days. The HF group was then fed with an HF diet and treated with dimethyl sulfoxide while the SP group was fed with an HF diet and treated with SP600125 (50 mg/kg) once per day. RESULTS. Feeding rats with an HF diet established a model of NASH, with varying degrees of hepatic steatosis and hepatic inflammation. SP600125 treatment substantially decreased the incidence of insulin resistance, reduced lipotoxicity, inhibited oxidative stress and alleviated hepatocellular injury. CONCLUSIONS. SP600125 has the potential to remarkably attenuate steatosis and inflammation and may be a novel therapeutic drug against NASH.

Modified synthetic siRNA targeting tissue inhibitor of metalloproteinase-2 inhibits hepatic fibrogenesis in rats.

BACKGROUND/AIMS: Fibrosis occurs in most chronic liver injuries and results from changes in the balance between synthesis and degradation of extracellular matrix (ECM) components. Matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) are known to regulate the ECM turnover. We investigate the effect of modified synthetic small interfering RNA (siRNA) targeting TIMP-2 in rat model of liver fibrosis. METHODS: Rat hepatic fibrosis was induced by CCl4 for 8 weeks. After the 2-week CCl4 injection period, rats in the three siRNA groups simultaneously received a different dosage (0.05, 0.1 and 0.2 mg.kg(-1), respectively) of modified synthetic siRNA targeting TIMP-2 via the tail vein every 3 days for 6 weeks. The pathological changes in liver tissues were observed by light microscopy and transmission electron microscopy. Portal vein pressure and proliferating cell nuclear antigen were measured. Expression of TIMP-2, MMP-2, MT1-MMP, MMP-13, hepatocyte growth factor, collagen type I, collagen type III and alpha-SMA were evaluated by quantitative real-time polymerase chain reaction or Western blotting or gelatin zymography. RESULTS: Modified synthetic siRNA targeting TIMP-2 induced a dose-dependent inhibition of the TIMP-2 expression in the rat model of liver fibrosis with a similar trend in MMP-2 and MT1-MMP, but an increase in MMP-13. Rats administered siRNA targeting TIMP-2 showed promotion of ECM degradation, reduction in activated hepatic stellate cells and enhancement of hepatocyte regeneration. Furthermore, portal hypertension was also ameliorated after treatment with siRNA targeting TIMP-2. CONCLUSIONS: Knock-down of TIMP-2 expression attenuates CCl4-induced liver fibrosis and is a potential pharmacological target for gene therapy in liver fibrosis.